Fast-Atom-Bombardment

Here the source of primary beam is xenon atoms, which because of higher mass and momentum provides better sensitivity than that of the beam of argon atoms used in the original discovery. The xenon atoms are first ionized in the FAB gun by collisions with electrons that are moving in a saddle-field configuration. 

Ionized xenon atoms are accelerated to the required potential (2 to 10 kV). Next, the fast-moving Xe+ ions are neutralized in a dense cloud of excess neutral gas atoms to generate a continuous stream of high-translational-energy xenon atoms. Any residual undischarged ions are deflected with a positive potential onto a deflector plate. 

The detection sensitivity in FAB-MS analysis is a function of the chemical composition of the sample-matrix mixture and of the presence of other unwanted impurities. The surfactancy of a solute and the matrix also influences the analyte signal. Because hydrophobic compounds tend to occupy the upper layer of the hydrophilic matrix, they are ionized preferentially relative to the hydrophilic compounds. In contrast, hydrophilic compounds exhibit poor response, because they remain buried within the lower layers of the matrix. Also, alkali salts are known to suppress ionization. Therefore, to obtain a sufficiently high ion current of the target compound, the matrix surface composition must be optimized by adjusting its pH or by the addition of surfactants. 

In early mass spectrometry applications of lasers, the sample was irradiated directly by a laser beam to desorb intact sample-related ions [27]. In this direct mode, termed laser desorption/ionization (LDI), the extent of energy transfer is, however, difficult to control and often leads to excessive thermal degradation. Also, not all compounds absorb radiation at the laser wavelength and thus are not amenable to LDI. Only those compounds that have mass below 1000 Da can be analyzed by LDI. Analytical sensitivity is also poor. A key contribution of LDI experiments is the observation that the desorption efficiency of amino acids and peptides that absorb the laser fight beam is greater than those without the chromophore [28]. IR lasers (e.g., an Nd YAG laser at 1.06 p m and a pulsed CO2 laser at 10.6 pm) and UV lasers (frequency-quadrapled Nd YAG laser at 266 nm) have aU been used. The detection of malaria parasites in blood by LDI with an N2 laser has been demonstrated [29]. 

Matrix-assisted laser desorption/ionization (MALDl) was developed nearly simultaneously by two research groups, Karas and Hillenkamp [30] in Germany and Tanaka and co-workers in Japan [31]. Tanaka is a recipient of the 2002 Nobel Prize in Chenfistry. MALDl has significantly revolutionized approaches to the study of large biopolymers. That landmark development has provided a uiuque opportunity to apply mass spectrometry to the analysis of proteins and other biomolecules with masses in excess of 200 kDa and with an improved sensitivity of several orders of magnitude. 

FAB is a relatively soft ionization technique using a high-energy (4,000- to 10,000-eV) beam of atoms, typically argon or xenon. The material to be analyzed is mixed with a nonvolatile matrix chemical. Common matrices include glycerol, thioglycerol, 3-nitrobenzyl alcohol (3-NBA), 18-crown-6 ether, 2-nitrophenyloctyl ether, sulfolane, diethanolamine, and triethanolamine. 

FAB produces primarily intact protonated molecules denoted as [M + H]+ in positive ion spectra and deprotonated molecules such as [M - H] in negative ion spectra. The nature of its ionization products places it close to ESI and MALDI. 

Cl is not the only ionization technique where this aspect of interpretation must be considered carefully fast-atom bombardment, thermospray, electrospray and atmospheric-pressure chemical ionization, described below in Sections 3.2.3, 4.6, 4.7 and 4.8, respectively, all produce adducts in the molecular ion region of their spectra. 

Both El and Cl require the analyte of interest to be in the vapour phase before ionization can take place and this precludes the study of a significant number of polar, involatile and thermally labile analytes. 

Fast-atom bombardment (FAB) is one of a number of ionization techniques which utilize a matrix material, in which the analyte is dissolved, to transfer sufficient energy to the analyte to facilitate ionization. In FAB, the matrix material is a liquid, such as glycerol, and the energy for ionization is provided by a high-energy atom (usually xenon) or, more recently, an ion (Cs+) beam. In conventional FAB, the solution of analyte in the matrix material is applied to the end of a probe which is placed in the source of the mass spectrometer where it is bombarded with the atom/ion beam. 

In contrast to conventional FAB where the analyte is dissolved in the matrix material, it has been found that FAB performance can be obtained when the mobile phase contains as little as 5% of the matrix material, thus reducing the chemical background associated with the technique. It should be noted that if the matrix material is added before the column it may have an effect on the separation achieved. 

Why might the addition of the FAB matrix to the HPLC mobile phase have an effect on the separation obtained  

FAB mass spectrometric analyses require a high-energy atom beam, usually 6-10 keV. The atom beam, typically xenon, is directed at the sample which is dissolved in a matrix. Typical matrices include glycerol, thioglycerol, m-mtrobcnzyl alcohol and a mixture of dithiothreitol and dithioerythritol. The continual bombardment of the sample/matrix mixture results in desorption of both species. Ions are formed, either as pre-formed ions from the matrix or in the gas phase immediately above the sample surface. 

Principles and Characteristics In the early mass-spectrometric ionisation techniques, such as El and Cl, the sample needs to be present in the ionisation source in its gaseous phase. Volatilisation by applying heat renders more difficult the analysis of thermally labile and involatile compounds, including highly polar samples and those of very high molecular mass. Although chemical derivatisation may be used to improve volatility and thermal stability, many compounds have eluded mass-spectrometric analysis until the emergence of fast atom bombardment (FAB) [72]. 

FAB-MS is a renewed old technique, first described in 1966 as molecular beam for solid analysis (MBSA) [73], and later (1981) further extended with a liquid matrix [72,74], The FAB experiment is closely related to 

Generally FAB produces protonated, MH+, or depro-tonated, (M — H) , quasi-molecular ions with a little excess energy which will sometimes produce fragment ions of low intensity. FAB is therefore a mild to soft ionisation technique which produces primarily molecular weight information and some structural information. Positive and negative ionisation mass spectra are produced with equal facility. FAB was originally used with magnetic sector mass spectrometers, but lately mainly with quadrupole mass spectrometers (Table 6.10). 

Sample preparation for FAB is primarily dissolving the analyte in a liquid matrix. The matrix plays 

The scope of the matrix is not only to transport and maintain the sample in the high-vacuum region of the source of the mass spectrometer, but also it appears to be necessary for the ion formation process. The matrix is often mixed with small quantities of an electrolyte to improve the results. Matrix and electrolyte tend to complicate FAB and FIB/LSIMS spectra, or at least are viewed by the analyst as essentially complicating the matter. 

Note Besides their momentum, the nature of the primary particles is of minor relevance for the spectral appearance [28] because little difference is observed between FAB and LSIMS spectra. Otherwise not explicitly distinguished from LSIMS, here the usage of the term FAB will also implicate LSIMS. 

MALDI was introduced in the 1980s by Karas and Hillenkamp [7, 59]. It has quickly gained popularity because it enables identification of biomolecules within a broad mass range from a few hundred daltons to several tens of kilodaltons. In particular, it is applied 

In addition to its usefulness in the analysis of a variety of analytes, MALDI-MS also possesses the advantage of rapid and simple sample preparation. Easy sample preparation 

Overall, the MALDI matrix possesses multiple functions [7, 59-62, 64-67]  

When discussing matrix-free LDI strategies, we should also mention one more related approach that resonated in the specialist literature over the past two decades. In desorption/ ionization on silicon (DIOS), a nanostructured silicon chip is utilized as the SALDI-assisting material [81]. After depositing sample solution on such a chip, the sample is ready for LDI-MS analysis. Furthermore, DIOS chips are compatible with microfluidic and microreactor systems [92, 93]. Thus, DIOS-MS has occasionally been implemented in TRMS-related measurements (see also Chapters 7 and 13). 

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A connnon feature of all mass spectrometers is the need to generate ions. Over the years a variety of ion sources have been developed. The physical chemistry and chemical physics communities have generally worked on gaseous and/or relatively volatile samples and thus have relied extensively on the two traditional ionization methods, electron ionization (El) and photoionization (PI). Other ionization sources, developed principally for analytical work, have recently started to be used in physical chemistry research. These include fast-atom bombardment (FAB), matrix-assisted laser desorption ionization (MALDI) and electrospray ionization (ES). 

FigureBl.7.2. Schematic representations of alternative ionization methods to El and PI (a) fast-atom bombardment in which a beam of keV atoms desorbs solute from a matrix (b) matrix-assisted laser desorption ionization and (c) electrospray ionization.

Barber N, Bordoll R S, Elliot G J, Sedgwiok R D and Tyler A N 1982 Fast atom bombardment mass speotrometry Anal. Chem. 54 645A-57A... 

Fast-Atom Bombardment (FAB) and Liquid-Phase Secondary Ion Mass Spectrometry (LSIMS) Ionization... 

A big step forward came with the discovery that bombardment of a liquid target surface by abeam of fast atoms caused continuous desorption of ions that were characteristic of the liquid. Where this liquid consisted of a sample substance dissolved in a solvent of low volatility (a matrix), both positive and negative molecular or quasi-molecular ions characteristic of the sample were produced. The process quickly became known by the acronym FAB (fast-atom bombardment) and for its then-fabulous results on substances that had hitherto proved intractable. Later, it was found that a primary incident beam of fast ions could be used instead, and a more generally descriptive term, LSIMS (liquid secondary ion mass spectrometry) has come into use. However, note that purists still regard and refer to both FAB and LSIMS as simply facets of the original SIMS. In practice, any of the acronyms can be used, but FAB and LSIMS are more descriptive when referring to the primary atom or ion beam. 

The basic principles of fast-atom bombardment (FAB) and liquid-phase secondary ion mass spectrometry (LSIMS) are discussed only briefly here because a fuller description appears in Chapter 4. This chapter focuses on the use of FAB/LSIMS as part of an interface between a liquid chromatograph (LC) and a mass spectrometer (MS), although some theory is presented. 

The LC/TOF instmment was designed specifically for use with the effluent flowing from LC columns, but it can be used also with static solutions. The initial problem with either of these inlets revolves around how to remove the solvent without affecting the substrate (solute) dissolved in it. Without this step, upon ionization, the large excess of ionized solvent molecules would make it difficult if not impossible to observe ions due only to the substrate. Combined inlet/ionization systems are ideal for this purpose. For example, dynamic fast-atom bombardment (FAB), plas-maspray, thermospray, atmospheric-pressure chemical ionization (APCI), and electrospray (ES)... 

Some mild methods of ionization (e.g., chemical ionization. Cl fast-atom bombardment, FAB electrospray, ES) provide molecular or quasi-molecular ions with so little excess of energy that little or no fragmentation takes place. Thus, there are few, if any, normal fragment ions, and metastable ions are virtually nonexistent. Although these mild ionization techniques are ideal for yielding molecular mass information, they are almost useless for providing details of molecular structure, a decided disadvantage. 

This method is still in use but is not described in this book because it has been superseded by more recent developments, such as particle beam and electrospray. These newer techniques have no moving parts, are quite robust, and can handle a wide variety of compound types. Chapters 8 through 13 describe these newer ionization techniques, including electrospray, atmospheric pressure ionization, plasmaspray, thermospray, dynamic fast-atom bombardment (FAB), and particle beam. 

To achieve sufficient vapor pressure for El and Cl, a nonvolatile liquid will have to be heated strongly, but this heating may lead to its thermal degradation. If thermal instability is a problem, then inlet/ionization systems need to be considered, since these do not require prevolatilization of the sample before mass spectrometric analysis. This problem has led to the development of inlet/ionization systems that can operate at atmospheric pressure and ambient temperatures. Successive developments have led to the introduction of techniques such as fast-atom bombardment (FAB), fast-ion bombardment (FIB), dynamic FAB, thermospray, plasmaspray, electrospray, and APCI. Only the last two techniques are in common use. Further aspects of liquids in their role as solvents for samples are considered below. 

In fast-atom bombardment (FAB), an atom gun is used to project heavy, fast atoms (often argon or xenon) onto the surface of a target solution (matrix). 

As with fast atoms, bombardment of the matrix with fast ions causes very similar desorption of ions and neutrals. 

LC can be combined with all kinds of mass spectrometers, but for practical reasons only quadrapolar, magnetic/electric-sector, and TOP instruments are in wide use. A variety of interfaces are used, including thermospray, plasmaspray, electrospray, dynamic fast-atom bombardment (FAB), particle beam, and moving belt. 

Fast-atom bombardment (FAB) is an ionization technique that produces a protonated or deprotonated molecular ion, hence a molecular mass for the sample. It can be used for analysis of peptides up to m/z about 5000. 

Desorption ionization (DI). General term to encompass the various procedures (e.g., secondary ion mass spectrometry, fast-atom bombardment, californium fission fragment desorption, thermal desorption) in which ions are generated directly from a solid or liquid sample by energy input. Experimental conditions must be clearly stated. 

Caprioli, R.M., Continuous-Flow Fast Atom Bombardment Mass Spectrometry, Wiley, New York, 1990. 

El = electron ionization. Cl = chemical ionization TSP = thermospray FAB = fast atom bombardment FD = field desorption,... 

Mass spectral analysis of quaternary ammonium compounds can be achieved by fast-atom bombardment (fab) ms (189,190). This technique rehes on bombarding a solution of the molecule, usually in glycerol [56-81-5] or y -nitroben2yl alcohol [619-25-0], with argon and detecting the parent cation plus a proton (MH ). A more recent technique has been reported (191), in which information on the stmcture of the quaternary compounds is obtained indirectly through cluster-ion formation detected via Hquid secondary ion mass spectrometry (Isims) experiments. 

Physical Chemical Characterization. Thiamine, its derivatives, and its degradation products have been fully characterized by spectroscopic methods (9,10). The ultraviolet spectmm of thiamine shows pH-dependent maxima (11). H, and nuclear magnetic resonance spectra show protonation occurs at the 1-nitrogen, and not the 4-amino position (12—14). The H spectmm in D2O shows no resonance for the thiazole 2-hydrogen, as this is acidic and readily exchanged via formation of the thiazole yUd (13) an important intermediate in the biochemical functions of thiamine. Recent work has revised the piC values for the two ionization reactions to 4.8 and 18 respectively (9,10,15). The mass spectmm of thiamine hydrochloride shows no molecular ion under standard electron impact ionization conditions, but fast atom bombardment and chemical ionization allow observation of both an intense peak for the patent cation and its major fragmentation ion, the pyrimidinylmethyl cation (16). 

The analysis of penicillins by mass spectrometry (qv) has developed with the advent of novel techniques such as fast atom bombardment. The use of soft ionization techniques has enabled the analysis of thermally labile nonvolatile compounds. These techniques have proven extremely valuable in providing abundant molecular weight information from underivatized penicillins, both as free acids and as metal salts (15). 

One of the reasons for lack offlterature was probably because environmental analysis depends heavily on gas chromatography/mass spectrometry, which is not suitable for most dyes because of their lack of volatility (254). However, significant progress is being made in analyzing nonvolatile dyes by newer mass spectral methods such as fast atom bombardment (EAB), desorption chemical ionization, thermospray ionization, etc. 

Mass speetrometry has been used to eharaeterize mieroeystins using the method of fast-atom bombardment (FAB) ionization and MS/MS. Anatoxin-a has been analysed by MS in eombination with gas ehromatography in bloom and water samples, and in benthie eyanobaeterial material and stomaeh eontents of poisoned animals.Reeently, liquid ehromatography (LC) linked to MS has been employed to analyse mieroeystins, where FAB-MS and atmospherie-pressiire ionization (API-MS) have been used, and anatoxin-a, where thermospray (TSP-MS) was iised. ... 

FABMS Fast-atom bombardment mass spectrometry... 

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